Despite recent advances in our knowledge of the neural, metabolic and genetic controls of food intake and body weight regulation, the causes of obesity remain elusive and compelling explanations about how changes in body physiology or genetics might produce the current obesity epidemic have not been forthcoming. The present application approaches the problem from a novel theoretical formulation that links the efficiency of the regulatory control of intake and body weight to a relatively simple form of Pavlovian conditioning. Within this framework, consuming sweet-tasting substances (such as artificial sweeteners) which contain few or no calories has the effect of degrading the normal ability of sweet orosensory cues to predict calories. As a consequence of weakening this predictive relationship, sweet-tasting foods that contain calories become less able to evoke the compensatory physiological responses that underlie tight regulation. Preliminary results suggest that one mechanism by which exposure to such nonpredictive relationships may impair energy regulation is through a disruption of cephalic phase physiological responses. Studies are proposed to determine the relationship between cephalic phase responses and energy dysregulation produced by nonpredictive experience with sweet tastes and calories. In addition, we determine how the magnitude and impact of this experiential variable interacts with other environmental variables, including the composition of the maintenance diet and the duration of exposure to the nonpredictive diets. Finally, we test whether exposure to other dietary experiences, such as consumption of products manufactured with fat substitutes, which degrade the ability of tastes to predict calories produce similar effects on body weight regulation. Changes in the food environment in the U.S. over the past 25 - 30 years may have increased exposure to diets in which the sensory properties of a food are not predictive of its caloric consequences. The work described in the present proposal examines specific mechanisms by which this type of disruption predictive relationships could contribute to energy dysregulation; and the experiments may not only identify circumstances under which energy dysregulation occurs, but may also to identify potential approaches to reversing such impairment. Given the rapidity with which overweight and obesity continue to increase, identifying such novel approaches is becoming increasingly critical [unreadable] [unreadable] [unreadable]